Download Cranial nerve palsies in childhood

Eye (2015) 29, 246–251
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CAMBRIDGE OPHTHALMOLOGICAL SYMPOSIUM
1
Department of
Ophthalmology, BC
Children’s Hospital,
Vancouver, British
Columbia, Canada
2
Department of
Ophthalmology and Visual
Sciences, University of
British Columbia,
Vancouver, British
Columbia, Canada
Correspondence:
CJ Lyons, Department of
Ophthalmology, BC
Children’s Hospital, Room
A136, 4480 Oak Street,
Vancouver, British Columbia
V6H 3V4, Canada
Tel: +1 604 875 3117;
Fax: +1 604 875 3561.
E-mail: [email protected]
3
These authors contributed
equally to this work.
Received: 15 October 2014
Accepted: 24 October 2014
Published online: 9 January
2015
Cranial nerve palsies
in childhood
CJ Lyons1,2, F Godoy1,2,3 and E ALQahtani1,2,3
Abstract
in his/her impressive ability for repair, altering
the clinical presentation of cranial nerve paresis
in childhood. In this brief review of cranial
nerve paresis in childhood we highlight some of
these differences.
We previously reported our experience with
IIIrd nerve palsy in children,2 a series of 18
children presenting under 15 years of age. The
causes are shown in Table 1. As in other larger
pediatric series,3 congenital and trauma were
the most common aetiological factors. The
frequency of associated neurological
abnormalities (arachnoid cyst, optic nerve
hypoplasia, and so on) supported the
recommendation of neuroimaging of all
children presenting with congenital or
acquired cranial nerve III palsy. Notable
features in our series were the almost
universal presence of aberrant regeneration
because of misrouting of regenerating III fibres
in congenital palsy (5 of 6 (83%)) and the
frequent presence of pupil involvement that,
in contrast to the adult, did not suggest an
increased likelihood of a compressive
aetiology. As in Adie’s pupil, symptomatic
mydriasis can be treated with Pilocarpine 0.1%
drops in the affected eye. In addition, like
Adie’s pupil, the mydriatic pupil of III palsy is
frequently observed to become miotic, often
over a period of years.
Congenital III palsy may present with
complete ptosis and ophthalmoplegia or a
partial palsy with or without aberrant
regeneration. The degree of paralysis and
subsequent recovery determines the likelihood
of achieving a reasonable visual acuity in the
affected eye; satisfactory alignment with the
use of an anomalous head posture may be
associated with a good visual outcome. This
was the case in 6 of our patients (33%). Other
important amblyogenic factors include
reduced accommodation in the affected eye. In
the presence of underlying hypermetropia, so
common in children, this is equivalent to
penalization of the affected eye. Correction of
the hypermetropia and use of a bifocal lens for
We review ocular motor cranial nerve palsies
in childhood and highlight many of the
features that differentiate these from their
occurrence in adulthood. The clinical
characteristics of cranial nerve palsies in
childhood are affected by the child’s
impressive ability to repair and regenerate
after injury. Thus, aberrant regeneration is
very common after congenital III palsy;
Duane syndrome, the result of early repair
after congenital VI palsy, is invariably
associated with retraction of the globe in
adduction related to the innervation of the
lateral rectus by the III nerve causing cocontraction in adduction. Clinical features
that may be of concern in adulthood may not
be relevant in childhood; whereas the
presence of mydriasis in III palsy suggests a
compressive aetiology in adults, this is not
the case in children. However, the frequency
of associated CNS abnormalities in III palsy
and the risk of tumour in VI palsy can be
indications for early neuroimaging
depending on presenting features elicited
through a careful history and clinical
examination. The latter should include the
neighbouring cranial nerves. We discuss the
impact of our evolving knowledge of
congenital cranial dysinnervation syndromes
on this field.
Eye (2015) 29, 246–251; doi:10.1038/eye.2014.292;
published online 9 January 2015
Introduction
Palsies of cranial nerves III, IV, and VI are rare
in childhood, with an estimated incidence of 7.6
per 100 000.1 The affected child differs from the
adult in several ways. In the presence of cranial
nerve paresis, the child’s developing visual
system is liable to develop strabismic,
deprivation, or anisometropic amblyopia.
Fusion and stereopsis may be reduced or
abolished. The child also differs from the adult
Cranial nerve palsies
CJ Lyons et al
247
Table 1 Causes of III palsy in childhood
Ng and
Congenital
Trauma
Tumour
Vascular
Meningitis
Idiopathic
Lyons2
Biglan and
33%
28%
22%
11%
6%
2%
colleagues3
38%
32%
11%
11%
Ng and Lyons2 and percentages from Biglan series.3
near is helpful, along with an appropriate occlusion
regime for the contralateral eye.
A congenital or acquired III palsy with subsequent
repair and aberrant regeneration should be
distinguished from the much more worrying history of
a previously normal child who has slowly (often over a
period of years) developed a III palsy, with progressive
ptosis and exotropia (with or without pupil signs)
but who has evidence of aberrant regeneration.
The temporal pattern of this ‘primary aberrant
regeneration’ should alert the clinician to the possibility
of nerve damage from a compressive process with
simultaneous ongoing repair. This is a classical sign of a
slow-growing lesion in the cavernous sinus such as a
schwannoma or meningioma.4 The corneal sensation
may also be decreased indicating concurrent Vth nerve
involvement. This clinical scenario should prompt
magnetic resonance imaging (MRI) of the brain with
particular attention to the cavernous sinus.
Neurofibromatosis 2, a tumour-suppressor mutation,
has a relative predilection for tumour formation in
cranial nerves III and V, probably because of their
relative bulk compared with cranial nerves IV and VI.
Rarely, repair does not result in resolution of III palsy
with or without aberrant regeneration. Instead,
children with oculomotor nerve paresis with cyclic
spasms have a history of unilateral congenital III palsy
with ptosis, esotropia, and mydriasis. Every 2 min or so,
bursts of III function result in elevation of the ptotic
eyelid as the globe starts to adduct and the pupil
constricts. This ‘spastic phase’ lasts B30 s before III
function reverts to the ‘paretic phase’.5 This condition,
sometimes also known as ‘Cyclical III palsy’, likely
results from disrupted repair processes following
congenital III; Miller6 demonstrated very similar
findings in two adults who had previously undergone
skull-base irradiation with subsequent repair, a process
that the author felt was similar to the development of
neuromyotonia.
In recent years, there has been a rapid evolution in our
understanding of the disorders formerly known as
congenital fibrosis of the extraocular muscles. These
disorders, identified as CFEOM 1–3, resulted in variable
manifestations of ptosis with vertical movement deficits
and reduction of horizontal eye movements. Pupillary
signs are occasionally evident as these disorders reflect
variable congenital involvement of the III nerve. We
examined an affected infant under general anaesthesia at
the age of 10 months and noted free forced duction
testing. The same examination repeated in this patient at
the age of 9 years showed marked restriction,
particularly in elevation. ‘Congenital Fibrosis’ is thus a
misnomer as the restrictive ‘fibrosis’ is a feature that
develops secondary to disuse related to primary
congenital dysinnervation.
The phenotypic patterns were named CFEOM 1–3, but
as is often the case in pediatric ophthalmology, the
underlying genetic mutations that arise anywhere from
the brainstem to the orbit are forcing a rethink of this
group of conditions that are now referred to as the
congenital cranial dysinnervation disorders (CCDDs)7,8
Fourth (trochlear) nerve palsy is the commonest
congenital cranial nerve palsy.1 Physically slender, with a
long intracranial course, this nerve is subject to traumatic
damage. Unilateral or bilateral fourth nerve palsy results
in characteristic motility patterns including elevation in
adduction, V-pattern related to reduced abduction force
in downgaze with unopposed adduction by the inferior
recti, and excyclotorsion. Chin-down head posture for
bilateral and contralateral head tilt for unilateral palsy
are noted, and the diagnosis is made clinically with
support from orthoptic testing that reveals large vertical
fusional ranges for long-standing or congenital cases.
Thus, neuroimaging is rarely indicated.
However, several imitators exist. In particular, the
craniofacial disorders are known to produce ocular
motility patterns that are virtually identical. Some
patients may also present with this characteristic ocular
motility pattern without overt craniofacial signs
(Figure 1). In the presence of an unexplained primary
V-pattern with bilateral superior oblique underaction or,
conversely, a primary A-pattern with bilateral superior
oblique overaction, we recommend a careful examination
of the lid fissure, as a marked mongoloid or antimongoloid slant may be the only indicator of underlying
ex- or in-cyclo rotation of the orbital contents as seen in
craniofacial disorders. An accompanying oblique
astigmatism may confirm this entity. Coronal cuts on
orbital MRI will highlight the lateral displacement of the
superior recti and medial displacement of the inferior
recti, superior displacement of the medial recti, and
inferior shift of the lateral recti, emphasizing the orbital
cause of this primary V-pattern ocular motility disorder.
An analogous condition has been described with primary
A-pattern with incyclotorsion of the orbital contents.9
Fourth nerve palsy imitations frequently go
undetected. Occasionally a Superior oblique tendon is
Eye
Cranial nerve palsies
CJ Lyons et al
248
Figure 1 (a) This 3-year-old boy does not have any facial features of craniofacial synostosis. (b) He presents with a V-pattern
exotropia with marked elevation of each eye in adduction, suggesting a diagnosis of bilateral superior oblique palsy. (c) Coronal
T2-weighted MRI shows excyclorotation of the orbital contents. Lines are drawn through the centre of the vertical recti on each side
emphasizing the muscle displacement. There is un-pairing of the horizontal yoke muscles, leading to elevation of the adducting eye
and depression of the abducting eye on each side. A full colour version of this figure is available at the Eye journal online.
found at surgery to be completely absent.10 In the past
few years, radiological techniques using higher-resolution
3T MRI have been used to identify the fourth nerve in
normal patients and those with congenital fourth nerve
palsy.11 A total of 97 patients with a history consistent
with congenital IV nerve palsy were reviewed: the
ipsilateral IVth nerve was absent in 73% of patients, with
variable ipsilateral superior oblique hypoplasia.
Eye
The authors suggested that congenital IVth nerve palsy,
a common and unexplained form of congenital cranial
nerve paresis, was also a form of CCDD.
Knapp12 wrote a classic series of papers regarding the
surgical management of IVth nerve palsy, emphasizing
the importance of careful preoperative measurements,
tailoring surgery to the gaze direction in which the
deviation is greatest through judicious use of rectus
Cranial nerve palsies
CJ Lyons et al
249
Table 2 Causes of VI nerve palsy in a series of 75 children who
had undergone neuroimaging (Lee et al14)
Neoplasm
Raised ICP
Trauma
Congenital
Inflammatory
Idiopathic, miscellaneous
45%
15%
12%
11%
7%
10%
recessions, inferior oblique weakening, and superior
oblique tuck.
Fells and his team13 reviewed the management of
bilateral superior oblique palsy and stressed the
importance of dealing with any significant torsion as a
primary procedure, using his modification of the Harada
Ito procedure. Failure to deal with the torsion was an
important barrier to a satisfactory fusion result in this
series. Identification of masked bilaterality and
appropriate planning for torsional correction are
important in preoperative surgical planning for bilateral
IVth nerve palsy.
Lee et al14 reported a series of 75 children with VIth
nerve palsy, all of whom had undergone neuroimaging.
(Table 2) They found that almost half of the cases were
due to neoplasm and suggested that neuroimaging
should be considered. Conversely, Holmes et al1 in their
population-based review of cranial nerve palsies in
children found that no case of intracranial neoplasia
presented as an isolated cranial nerve palsy. We
recommend neuroimaging for the majority of cases,
particularly if there is involvement of the neighbouring
cranial nerves. Illustrative patients (Figures 2 and 3) are
reminders that the VIth and Vth nerves are contiguous in
the cavernous sinus so that loss of corneal sensation
indicates pathology at that site. Conversely, the VIth and
VIIth nerves are contiguous in the pons and facial nerve
weakness accompanying VI palsy points to pontine
pathology.
Lee et al14 in their review of 75 children with VIth nerve
palsy who had undergone neuroimaging found that 11%
were congenital. In this number, they included children
with Duane Syndrome; it is true that Duane and Moebius
syndromes, which are both forms of CCDD, are types
of congenital VIth nerve paresis; Duane syndrome is a
congenital VIth nerve palsy with repair by the IIIrd nerve
and Mobius syndrome may present VIth nerve palsy or a
full-blown horizontal gaze palsy.
Sixth nerve palsy may complicate otitis media, an
association known as Gradenigo syndrome. In addition,
there may be venous or even cavernous sinus
thrombosis, making this complication of otitis media
potentially life-threatening.15 It is difficult to know
whether the current trend to withhold antibiotics for
Figure 2 (a) This 3-year-old boy was involved in a severe
motor vehicle accident; after a week in intensive care, he was
transferred to the ward. At that time he was noted to develop a
red left eye, prompting referral to ophthalmology. At 3 h after
referral, the redness had resolved but a left VIth nerve palsy was
evident. The ipsilateral corneal sensation was decreased,
indicating likely cavernous sinus compression of V and VI.
Neuroimaging and angiography (b) revealed a dissecting carotid
aneurysm causing Vth and VIth nerve compression within the
cavernous sinus. A full colour version of this figure is available
at the Eye journal online.
acute otitis media is contributing to a possible increased
incidence of severe complications such as those noted in
our report.
Benign idiopathic VIth nerve palsy is a condition
that is not uncommon in childhood; Mahoney and Liu16
reviewed 225 children with VIth nerve palsies and
found that 30 (13%) were in this group. Their mean
age was 3 years and 28 of the 30 had an MRI. In four
of the patients, the esotropia eventually became
comitant. Sturm and Schöffler17 reported a group
of 12 children followed up for over 9 years. Like
previous authors, they pointed out a preponderance
of girls affected by a left-sided palsy that resolved in
Eye
Cranial nerve palsies
CJ Lyons et al
250
compressive aetiology in adults, this is not the case in
children. However, the frequency of associated CNS
abnormalities in III palsy and the risk of tumour in VI
palsy can be indications for early neuroimaging
depending on presenting features elicited through a
careful history and clinical examination. The latter
should include the neighbouring cranial nerves.
Recent genetic and neuroradiological evidence, as well
as our evolving understanding of the genetic control of
the process of extraocular muscle innervation, have
highlighted the clinical entity of CCDD. Increasingly, we
realize that this group of disorders is an important
aetiological factor underlying the congenital cranial
nerve palsies.
Conflict of interest
The authors declare no conflict of interest.
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Figure 3 A 17-year-old girl presented with a left VIth nerve
palsy (a). Ipsilateral VIIth nerve function was decreased (b). MRI
showing a pontine glioma (c). A full colour version of this figure
is available at the Eye journal online.
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In summary, the clinical characteristics of cranial nerve
palsies in childhood are modified by the child’s capacity
for repair and regeneration after injury. Thus, aberrant
regeneration is very common after congenital III palsy;
Duane syndrome, a form of congenital VI palsy, is
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by the III nerve causing co-contraction in adduction,
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